Perforin - Granzyme
Utility: 1) Diagnostic screen for hemophagocytic lymphohistiocytosis (HLH).
2) Determination of intracellular perforin, granzyme A and granzyme B within cytolytic lymphocytes.
Specimen: 4 - 10 mL peripheral blood in sodium heparin (green top).
CPT codes: 86359, 86360, 86355, 86357, 88184, 88185 x 5, 88187.
Clinical indication/general description
HLH is a rare, life-threatening disorder characterized by excessive lymphocytic activation and cytokine secretion, macrophage activation, subsequent hemophagocytosis of blood cells and organ dysfunction. This disorder usually is triggered by viral infections and typically presents at a young age. All known genetic mutations associated with HLH occur in genes encoding proteins in natural killer (NK) cells and cytotoxic lymphocytes that are required to kill virally infected cells. Perforin, a pore-forming protein stored in cytotoxic granules and secreted by NK cells and cytotoxic lymphocytes, is required to kill virally infected and malignant cells. Mutations in perforin, as well as other granule-associated proteins, have been shown to cause HLH. Individuals with HLH also exhibit defective NK cell function.
The assay is designed to enumerate the percentage of NK cells (CD56+CD8-) and T cytotoxic cells (CD56-CD8+) expressing perforin, granzyme A and granzyme B. This assay can detect patients with HLH that lack perforin, and also evaluates the expression of cytotoxic molecules (perforin, granzyme A and granzyme B) in NK cells of patients with defective NK cell cytotoxic function.